Is ABCC6 p.Arg595Trp (c.1783C>T) pathogenic?

ABCC6 p.Arg595Trp (c.1783C>T) is classified Likely benign in ABCC6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-23). AlphaMissense: likely benign (0.1229); Rare (popmax 0.241%, afr).

How common is ABCC6 p.Arg595Trp (c.1783C>T) in the general population?

ABCC6 p.Arg595Trp (c.1783C>T) is rare (popmax 0.241%, afr) (gnomAD).

What do computational predictors say about ABCC6 p.Arg595Trp (c.1783C>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

ABCC6 p.Arg595Trp

c.1783C>T · rs150866831 · VCV736798

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.241%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP -0.89, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.241% African / African-American · 181/75,000 alleles

Filtering AF 0.213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.202%

Overall 0.0141% 228/1,613,214 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.241%	414
East Asian	0.0245%	4,077
Remaining individualsnot grpmax-eligible	0.0176%	5,678
Admixed American	0.01%	9,990
South Asian	0.0022%	45,480
European (non-Finnish)	0.00144%	69,390

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCC6
Protein: p.Arg595Trp
Coding: c.1783C>T
MANE Select: NM_001171
dbSNP: rs150866831
Type: single nucleotide variant
Location: chr16:16187208 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB

Full ABCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC6 p.Arg595Gln Uncertain significance ★★ ⚠ same residue
ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same type
ABCC6 c.2071-1G>A Likely pathogenic ★★ same type
ABCC6 c.2591-1G>T Likely pathogenic ★★ same type
ABCC6 c.2787+1G>T Pathogenic ★★ same type
ABCC6 c.3506+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC6 c.3507-1G>A Pathogenic ★★ same type
ABCC6 c.3507-2A>G Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcc6-p-arg595trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown